Thiophosphoric acid esters and a process for their manufacture



United States Patent THIOPHOSPHQR C ACID ESTERS AND A PROCESS FOR THEIRMANUFACTURE Walter Lorenz, Wuppertal-Vohwinkel, Gerhard Schrader,

Wuppertal-Cronenberg, and August Dorken, Wuppertal-Sonnborn, Germany,assignors to Farbenfabriken Bayer Aktiengesellschaft, Leverknsen,Germany, a coriteration of Germany No Drawing. Filed Jan. 27, 1959, Ser.No. 789,259 Claims priority, application Germany July 10, 1956 14Claims. (Cl. 260-461) This invention relates to and has as its objectsnew and useful thiophosphonic acid esters and their production.Generally the new inventive esters may be repre sented by the followingformula wherein R, R and R stand for alkyl radicals, R stands forhydrogen or an alkyl radical, the alkyl radicals being especially loweralkyl radicals containing 1 to 4 carbon atoms, z stands for zero or awhole number up to two, and the group CEh-HaH-MeS- -------9 S (O)(Oh-S-R CHr-S-P +MeHai a The starting materials, if they are1-alkyl-mercapto-2- halomethyl-4-alkylbenzenes are easily obtainablefrom the corresponding 1-alkyl-mercapto-4alkylbenzenes with formaldehydeand hydrochloric acid as it is described e.g-. in, the German patentspecification No. 569,569. Thesealkyl mercapto compounds furthermore maybe oxidizedby known methods to the corresponding sulfoxides or sulfones.The. first may be obtained by oxidizing the sulfides in glacial aceticacid with molar amounts of hydrogen peroxide at lower temperatures,whereas the sulfones are obtained by using an excessof hydrogen peroxide(at least 2 mols) at higher temperatures. The oxidation may also becarried out after the condensation with the1-alkyl-mercapto-phenyl-thiophosphoric acid esters has taken place.

2,938,919 Patented May 31, 1960 thiolphosphates and the alkyl-mercapto-(or alkyl-sulfoxylor alkyl-sulfonyl-)-halomethyl-(alkyl)=benzenespreferably may be carried out at slightly elevated temperatures, saybetween about 20 and C. and in the presence of an inert solvent.Suitable inert solvents in the sense of this invention are e.g. loweraliphatic alcohols, such as methanol or ethanol, lower aliphaticketones, such as acetone or methylethyl ketone, or aromatic hy'--drocarbons, such as benzene, toluene, and the like. As salts of the0.0-dialkylthiolor -thionothiolphosphoric acids which are especiallysuitable for the inventive re-- action, there may be named the alkalimetal salts or antmoniurn salts. As halomethyl-(alkyl)-phenylthioethers- (or their corresponding sulfoxides or sulfones), especial-- lythe chloromethyl compounds may be used.

The compounds of the present invention are generally valuableinsecticides and plant-protecting agents. They kill pests such asaphids, flies and mites and exhibit a: very remarkable systemic action.They are especially valuable contact insecticides with a remarkably lowtoxicity against mammals. The special advantage of the inventivecompounds consists also in their acaricidal activity and in that theyare especially active against the eggs of red mites. The application ofthese compounds should be carried out according to the use of otherknown phosphorous insecticides, i.e. in dilution or solution with solidor liquid carriers,.such as chalk, talc, bentonite, water, alcohols,liquid hydrocarbons, etc. The inventive compounds may further be used incombination with other known insecticides or pesticides, etc. Effectiveconcentrations of the compounds may vary also; generally concentrationsof 0. 0001% to 1.0% kill pests effectively. The combinations of thecompounds may be sprayed or dusted or otherwise brought in contact withpests or plants to be protected. They may also be used as aerosols.

As a special example for the utility of the inventive compounds theQO-diisopropyl-S [2- (meth'yl-mereapto) 4-tmethylpheny1-(1)l-methyl-dithiophosphate of the following formula (CHs):-CHO fi P-S-CH(OHM-GEO has been tested against black bean aphids, and the toxicity hasbeen determined on rats orally. The above ester is mixed with the sameamount of dimethyl formamide; to this solution 50% by weight of acommercial emulsifier consisting of a benzyl hydroxy diphenyl polyglycolether is added. This mixture is diluted with water to an emul-- sioncontaining 0.01% of active ingredient, and that com-- position killsblack bean aphids completely when in-- fected plants are sprayed withthis solution. Poisoned. baits when fed to rats are well tolerated up toan amount: of 1 g. active ingredient per kg. animal.

The activity of the-following compound was tested on dwarf zbeans(Phaseolus vulgaris). Plants,-

;- heavily infested withspider mites of the type Tetranychus' aithaeHanst. were sprayed to the run ofl with aqueous emulsions prepared asdescribed above. After 48 hours' Example 1 58 grams of the ammonium saltof 0.0-diethylthiolphosphoric acid are dissolved in 200 com. ofmethylethyl ketone. At a temperature of about 40 C., 58 grams of4-methyl-2-chloromethyl-thioanisol in 50 com. methylethyl ketone areadded while stirring. The reaction product is kept at a temperature ofabout 75 C. for 75 minutes while stirring. Then it is cooled and theammonium chloride is filtered off with suction. The solvent is removedby distillation in vacuo. The residue is taken up in ether, washed withwater and the etherical solution is dried over sodium sulfate. There areobtained 87 grams of the new ester of the formula S--CH| CaHsO S P-B-CH1CHIO At a pressure of 0.01 mm. the new ester distills at a temperatureof about 144 C.

The new ester shows a medium toxicity of about 100 mg./kg. on ratsorally. Spider mites are killed completely at concentrations of 0.01%

By exactly the same procedure but using instead of the ammonium salt of0.0-diethylthiol-phosphoric acid, the corresponding amount of theammonium salts of 0.0-dimethylor 0.0-diisopropyl-thiolphosphoric acid,and instead of the '4-methyl-2-chloro-methylthioanisol, also exactly thecorresponding molecular amount of 4-ethyl- 2-chloro-methylthionanisol or4-methyl-2-chloro-methylthiophenetole there are obtained the followingcom- Example 2 42 grams of'dried and filtered potassium carbonate aresuspended in 180 com. of methylethyl ketone. There are added at atemperature of about 50 C. 47 grams of diethyl-dithiophosphoric acid.Furthermore there are added while stirring at a temperature of 60 48grams of 4- methy1-2-chloromethyl-thioanisol (dissolved in 70 com.methylethyl ketone). After a reaction time of 4 hours at a temperatureof 65-70 C. the mixture is cooled to room temperature and the potassiumchloride is filtered off with suction. The solvent is then removed bydistillation. The residue is taken up in ccm. of ether andwashed withwater. After drying the etherical solution the ether 'is evaporated invacuum. There are obtained 85 grams of the new ester of theformula At apressure of 0.01 mm. the new ester boils at 127- 130' C. Spider mitesare killed completely with concentrations of about 0.01%.

By exactly the same way but using instead of0.0-diethyl-dithiophosphoric acid potassium salt, the correspondingmolecular amount of the corresponding diinethyl ester and instead of the4-methyl-2-chloromethylthioanisol, exactly the corresponding molecularamount of, 4 ethyl 2 chloromethyl-thioanisol or 4 methyl-2-chloromethylthiophenetole there are obtained the following compounds:

isopropyl-dithiophosphoric acid. Thereafter there is added a solution of48 grams 4-methyl-2-chloromethylthioanisol in 70 com. of methylethylketone during 20- minutes. The reaction product is kept for 3 hours at atemperature of about 65 Cjand then is worked up as described in Example2. There are obtained'87.5 grams of the new ester of the formula S-CH(cam-0H0 s Yield: 96% of the theoretical. Even in high vacuum the newester is not distillable without decomposition. The new ester shows atoxicity LD of 500-1000 mg./kg. on rats orally. 0.01% solutions killblack bean aphids completely.

Example 4 40 grams of the ammonium salt of 0.0-diethylthiolphosphoricacid are di Sfllved in 150 ccm. of methylethyl ketone. There is added ata temperature of about 30 C. asolutio'n 'of 44 grams of the sulfone ofthe following formula dissolved in 100 ccm. methylethyl ketone:

SOr-CHl (hHsQ Yield: 81% of the theoretical. After a short period theraw product is crystallized; M.P. 63 C. The new ester shows a toxicityof 100 mg./kg. (LD on rats orally. Spider mites are killed completelywith concentrations of about 0.1%

The above shown sulfone may be prepared as follows: 95 grams of2-chloromethyll-methylthio-anisol are dissolved in 240 m1. of glacialacetic acid. At a temperature of 50 C. there are added 250 ml. ofhydrogen peroxide (concentration 35%) within minutes. The reaction iscompleted by standing for another hour and half a 5 6 Wh le cool n the ufuric ys z and may be recrystallized (if necessary) from benzene; M.P.84 C.

Example 5 SO-OH| OHr-Cl The reaction mixture is kept for 5 hours at atemperature of 60 C. and then it is worked up in the usual manner. There'are obtained 73 grams of the new ester of the following formula SCL-CH:G H O l CH;

The new ester-shows a medium toxicity of 1000 mg./kg.

. .6 on rats orally. Mosquito larvae are killed completely withconcentrations of about 0.0001%.

The above shown sulfoxide may be prepared as follows: grams of2-chloro-methyl-4-methyl-thioanisol are dissolved in 240 ml. of glacialacetic acid. At 0 C. there are added within 1 hour ml. of hydrogenperoxide (concentration 35%). The reaction is completed within 2 /2hours and the acetic acid and water is distilled ofif in vacuum. Thesulfoxide remains as an oil and is pure enough for being further reactedaccording to the above example.

Example 6 0 coin.

52 grams (0.3 mol) of 4-methylmercapto-benzylchloride of B.P. 96.-98C./2 mm. Hg are added dropwise at 40- 50 C. to a suspension of 67 grams(0.33 mol) of diethyl-thiolphosphoric acid ammonium salt in 150 oem. ofacetone. The mixture is heated for a further hour to 50-60 C. tocomplete the reaction. The precipitated ammonium chloride is filteredoff with suction. and the filtrate poured into water. The oil is takenup in benzene, washed with water and a sodium bicarbonate solution,dried and distilled. 77 grams of thiolphosphoricacid-0.0-diethyl-S-4-methylmercapto-benzyl ester are obtained in theform of a yello w, thinly liquid oil of B.P. 124 C./0.0l mm. Hg. Yield:81.3% of the theoretical.

The ester shows atoxicity (LD of 10 mg/kg. on rats per os. Spider mitesare killed to 60% even with dilutions of l:100.000.

Example 7 30.5 grams (0.2 mol) of 4- methylmercaptorbenzylchloride areadded dropwise to a solution of 44 (0.22 mol) ofdiethyl-thionothiol-phosphoric acid ammonium salt in 100 ccmhof acetonestarting at a temperature of 20 C. After the slightly exothermicreaction subsides, the solution is heated to 5060 C. for one hour, thereaction product is then poured into water, the oil is taken up inbenzene, washed and dried. By distillation 56 grams of thionothiolphosphoric acid-Q0- die thyI-S-A-methyImercapto-benzyl ester of B.P.125 C./ 0.01 mm..Hg are obtained in the form of a pale yellow, almostcolorless oil. Yield: 87% of the theoretical.

The ester shows a toxicity (LD of 50 mg./kg. on rats per os. 0.001%solutions kill spider mites to 100%.

0 CiHa Example 8 omso-Q-orn-s- 30.6 grams of the ester obtainedaccording to Example 6 are dissolved in 75. ccm. of methanol and treatedwith 0.5 ccm. of 50% sulfuric acid. The calculated amount of ahigh-percent hydrogen peroxide is added dropwise with cooling at 40-50C., the solution is stirred for one hour during which it cools. Afterthe addition of water, the oil is taken up in benzene, washed with waterand dried; the solvent is distilled oil; 29.5 grams of thiolphosphorioacid-0.0-diethyl-S-4-methyl-sulfinyl-benzyl ester are obtained intheform of a pale yellow, water-insoluble oil which is not distillable.

The toxicity (LD of the ester lies at 20 mg./kg. on rats per os. At aconcentration of 0.01% the ester still shows a 100% actionagainst theeggs of the red spider.

'If the ester obtained according to Example 6 is oxidized, with thecalculated amount of potassium permanganate in 2,9ss,91a

diluted sulfuric acid there is obtained the ester of the followingformula oom- J CH. O UB P Example 9 8 OCgH;

O CiHt As described in Example 8, 25 grams of the ester obtainedaccording to Example 7 are oxidized in 50 ccm. of methanol in thepresence of a small amount of dilute sulfuric acid with the calculatedquantity of hydrogen peroxide. After working up in conventional manner25 grams of thionothiol-phosphoric acid-0.0-diethyl-S-4-methyl-sulfinyl-benzyl ester are obtained. The colorless to pale yellowester is water-insoluble and not distillable.

The toxicity (LD of the ester lies between to mg./kg. on rats per es.With concentrations of 1:100.000 spider mites and their eggs arecompletely killed. 7

Example 10 O OOH:

45 grams of ammonium dimethylthiolphosphate are dissolved in 150 ccm.ofacetone, and p-methyl-mercaptobenzyl-chloride of B.P. 59 C./0.01 mm.Hg is added dropwise at 40-35 C. The solution is subsequently heated to60 C. for a half hour. After cooling, the salt is filtered oif and thesolution is diluted with benzene and shaken out twice with water. Thebenzene solution is dried over sodium sulfate and the solvent removed invacuum. 41 grams (corresponding to 74% of the theoretical) of the newester are obtained in the form of an almost colorless oil.

Analysis.Calculated: P 11.13%; Found: P=9.76%; S=22.85%.

Example 11 S 0Ct 1l OClHrl 56 grams of ammoniumdiisopropyl-thinothiol-phosphate are dissolvedin 15 0 ccm. of acetone,and grams of p-methylmercapto-benzyl chloride of B.P. 59 C./ 0.01 mm. Hgare added dropwise at C. Working up is carried out as indicated inExample 10. 66 grams of the new ester are obtained in the form of a paleyellow oil which is clear soluble in cyclohexane. Yield: 99% of thetheoretical.

Analysis.Calculated: P=9.26%; S=28.77%. Found: P -8.73%; S=26.73%.

Example 12 magma? 0 CHI! 53 grams of ammonium diisopropyl-thiolphosphateare dissolved in 150 ccm. of acetone, and 35 grams ofpmethyl-mercapto-benzyl chloride of B.P. 59 C./ 0.01 mm. Hg are addeddropwise at C. The reaction mixture is heated to the boil under refluxon a water bath for lhour. Working up is carried out as described inExample 10. The new ester is obtained in the form of a pale yellow oil.Yield: 63 grams corresponding to 99% of the theoretical.

Analysis.--Calculated: P=9.73% S=20.15%, Found: P=8.94%; S=17.3 2%.

Weclaim: I l. A thiophosphoric acid ester of the following formula INC/OR1 3. A thiophosphoric acid ester of the following formula S-CH: CgHsO SP-S-CH 4. A thiophosphoric acid ester of the following formula CH O l 5.A thiophosphoric acid ester of the following formula S-CH (CHah-CHO S 6.A thiophosphoric acid ester of the following formula 7. A thiophosphoricacid ester of the following formula 8. A thiophosphoric acid ester ofthe following formula 5 0 0,11, ems-Q0 H,--si

o O1H| 9. A thiophosphoric acid ester of the following formula O O C2H|cmso-Q-cmw-K 9 10. A thiophosphoric acid ester of the following formula0 0 01H. CH:S0|CHr-S- \O C211; 5 11. A thiophosphoric acid ester of thefollowing formula S O 01H; OH=SOQGHQ-S 1 12. A thiophosphoric acid esterof the following formula OCH:

13. A thiophosphoric acid ester of the following formula S O oaH' i llCHaS-CHzSP\ O CaH7l 14. A thiophosphoric acid ester of the followingformula O C :H'li

References Cited in the file of this patent UNITED STATES PATENTS2,803,580 Metivier Aug. 20, 1957 Patent No,, 2,938,919

May 31, 1960 Walter llorenz et al.3

Patent should read a s corrected belo or appears in the printedspecification ng correction and that the said Letters Column 3, lines 25to 31 the formula should appear as shown below instead of as in thepatent:

1 SCH C H O column 5, lines 25 to 31, the formula should appear as shownbelow instead of as in the patent:

2 5 O SOg-CHg P-S-CH C H O column 7, line 49, for "thinothiol-" readthionothiol same column 7,

lines 60 to 64, shown below in stead of as in the patent the formulashould appear as CH3 H2S-P (SEAL) attest:

KARL a Lttesting Officer W and sealed this 10th day of January 1961.,

ROBERT C. WATSON Commissioner of Patents

1. A THIOPHOSPHORIC ACID ESTER OF THE FOLLOWING FORMULA